Septic shock is a serious syndrome which most often accompanies gram-negative, and sometimes gram-positive, bacteremia. However, septic shock may occur in virtually any typical infection, e.g., viral, fungal, and rickettsial; it may also result from severe trauma or tissue injury. For example, gram-negative rods such as Enterobacteriaceae and Pseudomonaceae are normally found in the digestive tract, however, these bacteria can invade the bloodstream of patients receiving immunosuppressive therapy; or patients who have experienced trauma, burns, major surgical procedures, or organ transplantations, or diseases such as cystic fibrosis, renal insufficiency and malignant neoplasms. Once the bacteria have invaded the bloodstream, they become capable of inducing septic shock.
Septic shock usually results from a series of events triggered by bacteremia during which bacterial cell wall substances (endotoxin in gram-negative organisms and peptidoglycan/teichoic acid complex in gram-positive organisms) cause excessive activation of the cytokine, complement, coagulation factor, kinin, and ACTH/endorphin systems. Eventually, overactivation of these various systems results in a series of self-induced cardiovascular and metabolic events that progress to a state of circulatory collapse, shock and organ dysfunction.
Incipient septic shock is characterized by body temperature extremes (hypothermia or fever), orthostatic blood pressure decrease, decreasing urine output, edema, falling serum albumin concentration, development of a metabolic acidosis, elevated serum lactate, thrombocytopenia, and the like. Overall, the current concept of septic shock is that the syndrome is caused by the overwhelming reaction of the immune system to infectious agents, thereby resulting in a profound release of inflammatory mediators into the bloodstream and into tissues. Accordingly, it is believed that these mediators are the direct cause of organ and tissue injury.
Septic shock typically advances in two stages. First, patients demonstrate symptoms characteristic of vasomotor effects that follow cytokine and ACTH/endorphin release, kallikrein/kinin system activation, and histamine release induced by bacterial cell wall components or toxins. Thereafter, the resultant circulatory changes and capillary damage cause microvascular dysfunction, a fall in intravascular blood volume, decline in cardiac output, disseminated intravascular coagulation, and organ dysfunction. Cytokines, therefore, are involved in the generation of sepsis and septic shock. Cytokines are intercellular mediators. For example, cytokines play a role in the generation of an immune response, such as in an immune response to an infection or infectious organism.
Capillary leak syndrome (CLS) occurs as a side effect of cardiovascular surgery in that cytokines and anaphylatoxins are generated as a consequence of the blood oxygenation procedures employed during surgery. Virtually all children, and 50-75% of adults, suffer from this syndrome during or after cardiovascular surgery. The vascular injury and organ impairment produced by CLS resemble the impairments produced in septic shock.
In general, conventional therapies for septic shock and CLS require intensive monitoring and care. Typically, the therapies are directed to the maintenance of blood pressure, organ perfusion and oxygenation. These therapies often involve assisted ventilation, and often include volume replacement with plasma expanders such as 5% albumin, isotonic saline, or lactated Ringer's solution. Sufficient volume is provided to raise the pulmonary capillary wedge pressure to the high normal range. When simple volume replacement is not sufficient, vasopressor compounds such as dopamine, dobutamine, or norepinephrine may be used. Antiinflammatory drugs such as methylprednisolone, sodium succinate and antiprostaglandins, for suppression of inflammatory damage, may be used as needed. Other therapies include antimicrobial agents, corticosteroids, anticoagulants, and diuretics.
The results achieved by these septic shock and (CLS) treatments are not always completely satisfactory. Antibiotic therapy may exacerbate toxic shock by inducing the release of bacterial cell wall materials and toxins. Vasopressors do not ameliorate shock or capillary wall damage. Volume replacement may result in edema and cardiac complications.
Acute renal failure is broadly defined as a rapid deterioration in renal function sufficient to result in accumulation of nitrogenous wastes in the body. The causes of such deterioration include renal hypoperfusion, obstructive uropathy, and intrinsic renal disease such as acute glomerulonephritis.
Release of large amounts of myoglobin into the circulation is a common cause of acute renal failure. A number of conditions may cause myoglobinuria, usually with the acute onset of weakness or paralysis: Crush injury or infarction of a large mass of muscle; excessive muscular contraction; acute idiopathic polymyositis and viral myositis; or, drugs and toxins.
Frequently, rhabdomyolysis and myoglobinuria are due to extensive trauma with crush injuries. However, nontraumatic rhabdomyolysis associated with increased muscle oxygen consumption (heat stroke, severe exercise, and seizures), decreased muscle energy production (hypokalemia, hypophosphatemia, and genetic enzymatic deficiencies), muscle ischemia (arterial insufficiency, drug overdosage with resultant coma and muscle compression), infections (influenza), and direct toxins (alcohol) also can produce rhabdomyolysis resulting in acute renal failure.
Thus, with any disease that results in rapid destruction of a large mass of striated muscle, myoglobin and other muscle proteins enter the bloodstream and may appear in the urine, whereupon the urine becomes dark red or burgundy colored. Myoglobin may be separated from hemoglobin by spectroscopy or radioimmunoassay. When myoglobinuria is severe, renal damage may ensue and lead to anuria.
The exact mechanism whereby myoglobinuria results in acute renal failure is uncertain. Most likely, the mechanism of renal damage is not simply a mechanical obstruction of the tubules by precipitated myoglobin. Typically, the treatment for acute renal failure corresponding with myoglobinuria addresses the underlying cause of the myoglobinuria, if remedial. The treatment for anuria would be the same as with anuria following surgical shock.
Some authors have discussed the possibility that whole blood, or at least certain blood components, be extracorporeally treated to preferentially remove certain materials present in the blood. Some authors have also addressed the use of silica-based materials in those treatments. However, all proposed silica-based materials have been chemically modified silica. The chemical modifications are directed to providing a silica material that will not lead to blood coagulation, and resultant clogging/failure of the silica column. It was believed that a device that utilized unmodified silica would lead to failure, since chemical modifications on the silica were understood to be necessary to accomplish the desired results. Chemical modification of silica is, however, an intricate process that adds significantly to the cost of the resultant materials. Further, the chemically modified silica materials have not been fully successful at providing the desired dual result of removing selected factors from blood, while avoiding clotting within, and resulting failure of, the silica-containing device. Accordingly, there has been a need for a cost efficient and effective silica material for use in removing selected factors from a patient's blood.